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AKS-452 is a biologically-engineered vaccine comprising an Fc fusion protein of the SARS-CoV-2 viral spike protein receptor binding domain antigen (Ag) and human IgG1 Fc (SP/RBD-Fc) in clinical development for the induction and augmentation of neutralizing IgG titers against SARS-CoV-2 viral infection to address the COVID-19 pandemic. The Fc moiety is designed to enhance immunogenicity by increasing uptake via Fc-receptors (FcγR) on Ag-presenting cells (APCs) and prolonging exposure due to neonatal Fc receptor (FcRn) recycling. AKS-452 induced approximately 20-fold greater neutralizing IgG titers in mice relative to those induced by SP/RBD without the Fc moiety and induced comparable long-term neutralizing titers with a single dose vs. two doses. To further enhance immunogenicity, AKS-452 was evaluated in formulations containing a panel of adjuvants in which the water-in-oil adjuvant, Montanide™ ISA 720, enhanced neutralizing IgG titers by approximately 7-fold after one and two doses in mice, including the neutralization of live SARS-CoV-2 virus infection of VERO-E6 cells. Furthermore, ISA 720-adjuvanted AKS-452 was immunogenic in rabbits and non-human primates (NHPs) and protected from infection and clinical symptoms with live SARS-CoV-2 virus in NHPs (USA-WA1/2020 viral strain) and the K18 human ACE2-trangenic (K18-huACE2-Tg) mouse (South African B.1.351 viral variant). These preclinical studies support the initiation of Phase I clinical studies with adjuvanted AKS-452 with the expectation that this room-temperature stable, Fc-fusion subunit vaccine can be rapidly and inexpensively manufactured to provide billions of doses per year especially in regions where the cold-chain is difficult to maintain.

Epistaxis is a common presenting complain with varied differentials. Our case is of epistaxis due to maxillary sinus vascular malformation which could be managed with embolization and endoscopic excision. Histopathologically, the lesion had features of metastatic renal cell carcinoma (RCC). A RCC metastatic lesion masquerading as a maxillary sinus vascular malformation (VM) has been extremely rare in published literature. We present this interesting case of maxillary sinus VM and also briefly review the relevant literature.

To address the coronavirus disease 2019 (COVID-19) pandemic caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a recombinant subunit vaccine, AKS-452, is being developed comprising an Fc fusion protein of the SARS-CoV-2 viral spike protein receptor binding domain (SP/RBD) antigen and human IgG1 Fc emulsified in the water-in-oil adjuvant, Montanide™ ISA 720. A single-center, open-label, phase I dose-finding and safety study was conducted with 60 healthy adults (18-65 years) receiving one or two doses 28 days apart of 22.5 µg, 45 µg, or 90 µg of AKS-452 (i.e., six cohorts, N = 10 subjects per cohort). Primary endpoints were safety and reactogenicity and secondary endpoints were immunogenicity assessments. No AEs ≥ 3, no SAEs attributable to AKS-452, and no SARS-CoV-2 viral infections occurred during the study. Seroconversion rates of anti-SARS-CoV-2 SP/RBD IgG titers in the 22.5, 45, and 90 µg cohorts at day 28 were 70%, 90%, and 100%, respectively, which all increased to 100% at day 56 (except 89% for the single-dose 22.5 µg cohort). All IgG titers were Th1-isotype skewed and efficiently bound mutant SP/RBD from several SARS-CoV-2 variants with strong neutralization potencies of live virus infection of cells (including alpha and delta variants). The favorable safety and immunogenicity profiles of this phase I study (ClinicalTrials.gov: NCT04681092) support phase II initiation of this room-temperature stable vaccine that can be rapidly and inexpensively manufactured to serve vaccination at a global scale without the need of a complex distribution or cold chain.

The role of endonasal endoscopic approach for pathologies in the paediatric population is evolving and has still not been accepted as standard of care in neurosurgery. It represents a challenge in terms of narrow access, instrument manipulation and adequate reconstruction of defects. We have described our experience in 49 cases from a single neurosurgical unit in paediatric skull base surgeries through this approach over the last 12 years. A case series of 59 paediatric skull base surgeries in 49 children through endoscopic endonasal route over the last 12 years is presented. The age ranges from 4 months to 18 years. Out of 49 cases, 22 cases were of craniopharyngiomas, 8 cases of pituitary adenomas, 5 cases with CSF rhinorrhea, 5 cases with meningoencephalocele, 3 cases of Rathke’s cleft cysts, 2 cases of odontoidectomy and 4 miscellaneous cases viz. mucocele, hypothalamic glioma, esthesioneuroblastoma and epidermoid. CSF leaks were repaired with free graft in the initial years and by vascularized flap more recently. The goal of surgery was achieved in all but two cases in whom the tumour excision was unsatisfactory due to failure of the cyst wall to collapse after decompression. Extent of tumour excision was not compromised by the choice of this approach. Revision surgery for CSF leak was required in three patients. Local vascularized nasoseptal flap has been possible even in very young patients and has now become the standard for reconstruction. In spite of the challenges posed by small nostrils and ill-developed sinuses in the paediatric age group, surgery from endoscopic endonasal corridor is possible to be carried out successfully in selected cases.

Background The diagnosis of Rathke cleft cysts (RCC) has increased in recent times as a result of improvements in imaging techniques; however, symptomatic patients are uncommon and accurate preoperative diagnosis may sometimes be difficult. The indications of surgical management protocol are evolving. We aim to provide a comprehensive review of clinical, imaging, and histopathologic features with operative management strategies along with outcome and prognosis in RCC. Methods A retrospective analysis (2003–2015) was performed of 58 consecutive cases of RCC seen in a surgical unit. Twenty-seven surgically treated symptomatic RCCs were further evaluated for their clinical presentation, imaging characteristics, surgical approaches, and intraoperative findings. Results Headache was the most common presenting complaint followed by visual deficit. Hormonal abnormality was observed in 13 patients. On magnetic resonance imaging, the characteristic intracystic nodule was identified in 6 patients. Transsphenoidal surgery for cyst excision was performed in all 27 patients with an endoscopic route in 25 patients and radical excision was performed in 17 patients. The pituitary stalk and the normal gland were preserved in all patients. Headache improved in 96% of patients and visual field defect resolved in all. Around 46% had improvement of the anterior pituitary axis. New permanent hormone deficiency was not observed. The recurrence rate was 3.7% after a minimum of 18 months follow-up. Conclusions RCCs are an uncommon disease with a wide spectrum of clinical and radiologic features. Endonasal endoscopic transsphenoidal surgery provides excellent clinical and endocrinologic improvement. We believe that radical excision does not necessarily result in endocrinologic impairment and may have a better impact on recurrence and cyst resolution.

Hemangiopericytomas are vascular tumors arising from the capillary pericytes of Zimmermann present around the capillaries and post capillary venules. Known for a high rate of recurrence, a wide surgical excision is the treatment of choice of these tumors. These tumors are very vascular making surgical excision difficult. The coblation system has made it easier in resection of these vascular tumors. We present a case report of a extensive sinonasal hemangiopericytoma in a old man which was successfully resected with coblation technology.

Benign lesions of the skull base are common in the paediatric population, and are usually congenital in aetiology. Majority of these lesions are treated transcranially exposing the patients to a number of risks. Although endoscopic endonasal surgery (EES) helps avoid many of these potential morbidities, CSF leak with its attendant complication remains a big concern. This study reports the use of the Hadad flap in the reconstruction of skull base defects in infants to prevent this problem. The study was conducted on four infants with a mean age of 7 months, who underwent repairs for CSF leaks associated with congenital lesions like meningocele or meningoencephalocele, using the Hadad flap. Of the four patients, three cases were revision cases and one was primary where the patients presented with complaints such as nasal obstruction and watery nasal discharge. Post surgery, the infants were monitored for a mean period of 23 months and no major complications or recurrent CSF drainage were observed. Minor complications that were observed include vestibulitis and crusting in the nose. The utility of the Hadad flap in the reconstruction of skull base defects in the paediatric age group has been controversial while its utility in infants has not been studied in literature so far. We report here in our series four infant patients in whom we believe that the nasal septum and the skull base will develop proportionally to each other, hence lowering the chances of a short flap and eliminating the occurrence of future complications. The nasoseptal flap is an effective and safe technique for reconstructing skull base defects in infancy. It can be concluded that this technique does not have any potential effect on septal or craniofacial growth as the flap is harvested only on one side with normal mucosal cover on the other side. There is no posterior septectomy or any form of bony or cartilaginous resection that is performed, hence avoiding any effects on bony growth. No studies have been published in literature so far and to the best of our knowledge, this is the first report describing the efficacy of the nasoseptal flap in infants.

Aim: Endoscopic trans-nasal surgery has evolved a long way from the days of narrow corridors with high rates of cerebrospinal fluid (CSF) leak to the present state of HD optics with better tissue differentiation, extended approaches, and use of vascularized flaps for defect closure. Trans-nasal approach is an established technique for pituitary tumors practiced worldwide. However, trans-nasal endoscopic excision of suprasellar meningiomas provides a tougher challenge in terms of instrument manipulation, tumor excision with good visual outcome, and a robust defect closure to prevent CSF leaks. Materials and Methods: Out of 83 cases of midline anterior cranial fossa meningiomas operated over 14 years, our experience in 12 cases of suprasellar meningiomas for radical resection via the trans-nasal endoscopic route is discussed. Results: Amongst these, six were excised via primary extended endoscopic trans-sphenoidal surgery, four cases had a residual lesion or recurrence after primary transcranial surgery, and two cases involved a combined transcranial and extended endoscopic approach. Visual improvement along with resolution of headache was seen in all patients postoperatively. None of the patients had CSF leak requiring further repair. Syndrome of inappropriate antidiuretic hormone was found in one patient, which was transient and easily corrected. Conclusion: Trans-nasal endoscopic surgery for suprasellar meningiomas is an effective technique that provides results of tumor excision comparable to the transcranial approach in suitable cases. Visual outcome was found to be superior, and rates of CSF leak were remarkably reduced with vascularized flap. However, each case must be assessed individually and lateral extension beyond the optic canals with internal carotid artery encasement must be considered before planning surgery.

Cerebrospinal fluid (CSF) rhinorrhea occurs when there is a communication between subarachnoid space and sinonasal mucosa due to meningeal, osseous and mucosal defects in the cranial base leading to discharge of CSF from the nose. The risk of developing meningitis after CSF rhinorrhea may vary from 5.6 (Leech and Paterson in Lancet 1:1013-1016, 1973) to 60% (Eljarnel and Foy in Br J Neurosurg 5:275-279, 1991). Hence surgical management of CSF rhinorrhea is highly recommended. Transnasal endoscopic approach first described by Wigand in 1981, has been proven to be the approach of choice in comparison to intracranial and external nasal approach (Jones and Becker in Br Med J 322:122-123, 2001) in most cases. The next defining milestone was the pedicled naso septal vascularized flap described by Hadad et al. (Laryngoscope 116(10):1882-1886, 2006), which could be used to manage large defects. In the present study we assessed 243 cases of CSF rhinorrhea managed by transnasal endoscopic approach. We compared the various factors associated with CSF rhinorrhea and the correlation with the outcome of the surgical treatment. We also analyzed the different sites and techniques of surgical repair and have certain recommendations to improve the surgical outcome. The commonest cause of CSF leak was spontaneous (54.32%) and the commonest site was cribriform plate (43.24%). Patients presented most commonly with watery nasal discharge (82.3%). CT scan with cisternography or MR cisternography is the gold standard to identify the suspected site of leak. Out of 243 patients, 77.77% were operated using free grafts and 22.22% by flap repair. Results are comparable. Hence we would advise simple conservative technique with free grafts to reduce morbidity and shorten the postoperative recovery.

Craniopharyngiomas are dysontogenic tumors with benign histology but aggressive behavior. The surgical challenges posed by the tumor are well recognized. Neuroendoscopy has recently contributed to its surgical management. This study focuses on our experience in managing craniopharyngiomas in recent years, highlighting the role of combined endoscopic trans-ventricular and endonasal approach. Ninety-two patients have been treated for craniopharyngioma from 2000 to 2016 by the senior author. A total of 125 procedures, microsurgical (58) and endoscopic (67), were undertaken. Combined endoscopic approach was carried out in 18 of these patients, 16 children and 2 young adults. All of these patients presented with a large cystic suprasellar mass associated with hydrocephalus. In the first instance, they were treated with a transventricular endoscopic procedure to decompress the cystic component. This was followed by an endonasal transsphenoidal procedure for excision within the next 2 to 6 days. All these patients improved after the initial cyst decompression with relief of hydrocephalus while awaiting remaining tumor removal in a more elective setting. Gross total resection could be done in 84% of these patients. Diabetes insipidus was the most common postsurgical complication seen in 61% patients in the immediate period but was persistent in only two patients at 1-year follow-up. None of the children in this group developed morbid obesity. There was one case of CSF leak requiring repair after initial surgery. Peri-operative mortality was seen in one patient secondary to ventriculitis. The patients who benefit most from the combined approach are those who present with raised intracranial pressure secondary to a large tumor with cyst causing hydrocephalus. Intraventricular endoscopic cyst drainage allows resolution of hydrocephalus with restoration of normal intracranial pressure, gives time for proper preoperative work up, and has reduced incidence of CSF leak after transnasal surgery. Combined endoscopic approach thus gives a unique opportunity to remove these lesions more radically with less morbidity.

Seizure is a classical feature of intra axial brain parenchymal lesion. Simple bone cyst is an unusual bony pathology at skull base presenting with unexpected symptoms of complex partial seizures. Skull base neuro-endoscopy has managed such lesions more effectively with reduced post-operative morbidity as compared to transcranial approach. This case report discusses a 20-year-old male who presented with 3 episodes of seizure over a time period of 10 months. MRI brain revealed T1 hypo and T2 hyper intense cystic lesion in middle cranial fossa with no enhancement on contrast administration. CT scan showed cystic lesion involving greater wing and pterygoid plate of sphenoid on left side. CT cisternographic evaluation showed CSF outpouching in the sphenoid air sinus. Excision of the cystic lesion was carried out through endoscopic transmaxillary transpterygoid approach. Histopathological examination showed the lesion to be a simple bone cyst.

Pediatric brain tumors have always been challenging as well as intriguing in their anatomical, surgical, and postsurgical management-related issues. They are a heterogeneous set of pathologies involving different age groups in childhood and also differ widely from their adult counterparts as far as adjuvant therapies are concerned. Though neurosurgeons across the world are radical in surgery for most of the pediatric tumors, it can often be at the cost of future quality of life in suprasellar tumors. As the time has gone by, the pendulum has swung toward rather conservative and maximal safe surgical resections with adjuvant therapies coming to the forefront. Hence, the aim is to achieve a good quality of life for these children along with a control of tumor growth (rather than cure) and to again tackle the tumors, if required, once these children reach adolescence or adulthood. We have reviewed the literature for different pediatric suprasellar tumors and discussed their current management giving our perspective with illustrative cases.

Intracranial extension is the most dreaded complication of fungal sinusitis with high mortality rates. Fungal sinusitis is notorious for insidious and rapid intracranial spread. Therefore the most appropriate approach lies in timely diagnosis and early intervention.With various diagnostic modalities available; like CT scan, MRI, fungal stains, cultures and nasal endoscopy, the diagnosis has become much simpler, nevertheless, a high degree of clinical suspicion is a must.The treatment outcomes have now improved a lot, with the advancement in medical and surgical technology. The new antifungal agents and other drugs have immensely contributed to better results by minimizing the toxic side effects of the traditional drugs and showing better efficacy. The surgical approach, with the advent of endoscopes has led to successful outcomes.Despite this, in about 50% of the cases, since the host is immunocompromised, the prognosis is guarded and mortality rates of approximately 85 to 100% are noted.So, it is very important to treat intracranial extension of fungal sinusitis as a medical and surgical emergency.

Endonasal endoscopic surgery is now the preferred technique to tackle pituitary tumours. Our paper describes the stepwise endoscopic approach for surgeons embarking on pituitary surgery. It also highlights the common pitfalls encountered during surgery and the ways to avoid them. One must proceed in a gradual step- wise manner starting from simple exposure of the sphenoid sinus to complete endoscopic tumour removal so us to gain the neurosurgeon’s confidence as well as develop our own skills, confidence and ability to tackle complications. We use the endonasal paraseptal trans- sphenoidal approach. Surgery begins with gentle packing between the middle turbinate and septum to expose the anterior sphenoid wall and expose the sphenoid astium. The ostitum is then widened inferiorly and onto the opposite side to expose both sphenoid sinuses. The inter- sphenoid sinus and necessary mucosa is removed to expose the sella. We then use a bone flap technique or punches to open the sella. After incising the dura, tumour is removed with a suction curette. An endoscope holder facilitates the operation. The bone flap is replaced at the end of surgery to reconstruct the sella. This is especially important if a CSF leak is present. Nasal packing is usually not required.

Background: To study the clinical outcomes of Hadad-Bassagasteguy flap (HBF) in endonasal reconstruction of anterior skull base defects. Methods: We prospectively analyzed the demographic data & the outcome results particularly Post-operative CSF leak in 53 patients who underwent HBF in our hospital from February 2013 to June 2014. The early harvested flap was used to reconstruct anterior skull base defects among patients with high-flow on-table CSF leak. Post-operatively the patients were analyzed for CSF leak and bleeding. Results: Most of the study subjects were between21-50 years of age (73.6%). The mean age of the study subjects was 41.8±13.8 years. Male/female ratio of the study sample was 1.2 with 29 males and 24 females. Of the total 53 patients 46 (86.8%) has macro defects while 7 (13.2%) had micro defects. Non-secretary lesions were present in 60.4% (32/53) patients while secretary were present in 39.6% (21/53) patients. Cerebrospinal fluid leak was present in all the patients undergoing surgery and majority of them were put on lumbar drain, while bleeding was present in 49.1% patients. Of the total 53 patients only 2 had post-operative cerebrospinal fluid leak (2/53; 3.8%). Conclusions: Use of HB posterior nasal septal flap for reconstruction of anterior skull base among patients with high-flow intra-operative CSF leak has a remarkable impact in preventing post-operative CSF leak. Its applicability to wide patient-profiles with respect to age, size of defect, diagnosis is making it a versatile choice of reconstruction after endonasal anterior skull base surgeries.

Background The microsurgical transoral approach has traditionally been the preferred access for ventral decompression of the craniovertebral junction. This natural corridor, although direct, may be a challenging approach because of potential morbidities. The evolution of endoscopic methods in skull base surgeries has reduced morbidity and improved results. Endoscopic approaches are also being used for ventral decompression at the craniovertebral junction. Some technical modifications in this approach are described. Methods An endoscope is inserted endonasally for a panoramic view of the entire area of interest, from the sphenoid to second cervical vertebra. Image guidance systems are used in all cases to guide the resection. The soft palate is retracted away with a rubber catheter sling when both nasal and oral corridors are being used. Various mucosal flaps are raised for access and reconstruction. Actual decompression can be done through the nasal or oral corridors based on the relationship of the pathology to the palate. Reconstruction is done using standard principles with the vascularized flaps, fat, and fibrin glue. Results Reduced surgical morbidity by avoiding palatal split and good postoperative healing are some of the advantages of this modified endoscopic technique. Better surgical exposure and a wide perspective facilitate the decompression. However, as with all newer perspectives, a learning curve exists. Conclusions Used judiciously, this modified endoscopic approach to the craniovertebral junction and odontoid process is minimally invasive and adds to the surgeon's armamentarium.

Exogenous foreign bodies in the larygotracheo-bronchial tree, particularly in children are a common and challenging emergency for otolaryngologists and pediatricians. Common objects which may be inhaled as foreign bodies are groundnut seed, tamrind seed, chikoo seed, whistles (metallic or plastic), castor seed, betelnut, bones and metallic pins) Normal protective cough reflex usually prevents aspiration of these objects, but occasionally this reflex is unable to prevent aspiration of foreign bodies which thenge t impacted at some place in the laryngo-tracheo-bronchial tree. The difficulties in the diagnosis of tracheo-bronchial foreign bodies in children include non-availability of definite positive history of foreign body inhalation, unawareness or forgetfulness of such an incident on the part of parents, or out of sheer fear, the child may not disclose the incident. 2 Absence or lack of clinical features, or radiological signs also adds to the difficulty in diagnosis. Furthermore, cardio-respiratory failure is a real threat especially in children, and hence bronchoscopy should be done at the earliest. In most patients ulceration of the bronchial mucosa with haemoptysis, blood streaking or distal suppurat ion with or without bronchial stenosis occurs with long term foreign bodies) Foreign bodies that initially cause obstruction of moderate or marked degree result in pneumonitis, atelectasis, pulmonary suppurat ion and possible empyema if not removed. Occasionally slender, non-obstructive, non-irritating foreign bodies may remain 9 in the bronchial tree for prolonged periods without serious or pe~.~nent sequelae? Bronchoscopic removal of such long standing foreign bodies becomes difficult due to presence of a large amount of friable granulation tissue and excessive suppuration. 4

A foreign body that had penetrated the infratemporal fossa via the orbit was removed through the maxillary sinus.

A case of an unusally large dentigerous cyst in a13 years old female patient presenting with gross facial asymmetry involving the nose, eye and the mouth is reported. Subsequent management and review of the literature is discussed briefly.

A patient was referred for coronary artery bypass reoperation. After a left internal mammary artery was grafted to the left anterior descending coronary artery, the diseased but patent old saphenous vein graft was ligated. This resulted in severe myocardial failure, which was corrected only after restoration of flow through the old vein graft. We suggest the decision to ligate or replace an old vein graft should be individualized to avoid the risk of myocardial ischemia.